Dysregulation Of Gut Microbiota Research Articles

Immunomodulatory Mechanisms of Tea Leaf Polysaccharide in Mice with Cyclophosphamide-Induced Immunosuppression Based on Gut Flora and Metabolomics.

Tea polysaccharides (TPSs) are receiving increasing attention because of their diverse pharmacological and biological activities. Here, we explored the immunoregulatory mechanisms of TPSs from fresh tea leaves in a mouse model of cyclophosphamide (CTX)-induced immunosuppression in terms of gut microbiota and metabolites. We observed that TPSs significantly increased the body weight and alleviated CTX-induced thymus atrophy in the immunosuppressed mice; they also increased the plasma levels of immunoglobulins A and M, interleukin (IL) 1β, IL-6, inducible nitric oxide synthase, and tumor necrosis factor α. Furthermore, we conducted 16S rDNA sequencing of cecal contents, resulting in the acquisition of 5008 high-quality bacterial 16S rDNA gene reads from the sequencing of mouse fecal samples. By analyzing the data, we found that TPSs regulated the gut microbiota structure and diversity and alleviated the CTX-induced dysregulation of gut microbiota. The colonic contents of mice were subjected to analysis using the UPLC-Q-TOF/MS/MS technique for the purpose of untargeted metabolomics. In the course of our metabolite identification analysis, we identified a total of 2685 metabolites in positive ion mode and 1655 metabolites in negative ion mode. The analysis of these metabolites indicated that TPSs improved CTX-induced metabolic disorders by regulating the levels of metabolites related to tryptophan, arginine, and proline metabolism. In conclusion, TPSs can alleviate CTX-induced immunosuppression by regulating the structural composition of gut microbiota, indicating the applicability of TPSs as novel innate immune modulators in health foods or medicines.

Gut Microbiota Dysbiosis in the Pathogenesis of Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD)

: Metabolic-dysfunction-associated steatotic liver disease (MASLD), previously referred to as nonalcoholic fatty liver disease (NAFLD), affecting approximately 30% of the global population. Projections suggest that MASLD incidence may rise by up to 56% over the next decade. MASLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in the USA, France, UK, and other regions worldwide. The prevalence of MASLD and MASLD-related liver damage is expected to parallel the increasing rates of obesity and type 2 Diabetes Mellitus (T2DM) globally. The factors contributing to MASLD development and its progression to metabolic-dysfunction- associated steatohepatitis (MASH), fibrosis, cirrhosis, and HCC remain poorly understood. Evidence from cell-based, animal-based, and human-subject studies suggests that insulin resistance, endoplasmic reticulum stress, oxidative stress, impaired autophagy, genetics, epigenetics, reduced immune surveillance, increased gut inflammation, and gut dysbiosis are crucial events in MASLD pathogenesis. In recent years, dysregulation of gut microbiota has emerged as a potential mechanism implicated in MASLD and MASLD-related hepatocarcinogenesis. This review briefly outlines the mechanistic events significant for MASLD pathogenesis. Additionally, it offers insight into dysregulated gut microbiota and its correlation with MASLD and MASLD-related liver damage. Furthermore, it highlights pertinent questions for cell and microbiologists in the MASLD research field. It underscores the necessity for identifying factors leading to gut microbiome dysregulation in MASLD and MASH pathogenesis. Identifying these factors could aid in the development of novel strategies for managing MASLD and MASLD-related liver damage.

Punicalagin prevents the bone loss of diabetic mice induced by high‐fat diet via the metabolism of gut microbiota

AbstractDiabetes often induces bone loss and the dysregulation of gut microbiota (GM) is an important cause. Punicalagin (PU) was reported to regulate GM. Therefore, we hypothesized that PU could alleviate diabetes‐induced bone loss through GM and their metabolites. In this study, high‐fat diet‐induced diabetic mice showed bone erosion and poor biomechanical properties, while PU intake significantly improved the bone condition of diabetic mice. Further investigation revealed that the abundance of some beneficial bacteria, such as Akkermansia and Ruminiclostridium_9, was higher after PU intake and highly positively correlated with the concentrations of short‐chain fatty acids (SCFAs) and serum vitamin K2, respectively. In addition, these bacteria were associated with the levels of bone metabolism‐related markers such as procollagen type I N‐terminal propeptide (P1NP) and runt‐related transcription factor‐2 (Runx2). Mechanistically, PU, on the one hand, promotes the metabolism of SCFAs, thereby increasing the levels of bone synthesis markers and inhibiting the secretion of bone absorption markers. On the other hand, the higher level of vitamin K2 greatly accelerated bone mineralization and enhanced bone strength. This work provides a new perspective to explore the mechanism by which PU intervention alleviates diabetes‐induced bone loss by regulating the GM and their metabolic products.

Leech Poecilobdella manillensis protein extract ameliorated hyperuricemia by restoring gut microbiota dysregulation and affecting serum metabolites.

Hyperuricemia (HUA) is a public health concern that needs to be solved urgently. The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA; however, its underlying metabolic regulation remains unclear. To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism. A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections. The mice received oral drugs or saline. Additionally, 16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome, respectively. The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay. The protein extract of Poecilobdella manillensis lyophilized powder (49 mg/kg) showed an enhanced anti-trioxypurine ability than that of allopurinol (5 mg/kg) (P < 0.05). A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder, which included the genera of Prevotella, Delftia, Dialister, Akkermansia, Lactococcus, Escherichia_Shigella, Enterococcus, and Bacteroides. Furthermore, 22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder, which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism, sphingolipid metabolism, galactose metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites. The proteins in Poecilobdella manillensis powder were effective for HUA. Mechanistically, they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.

Oral matrine alleviates CCl4-induced liver fibrosis via preserved HSP72 from modulated gut microbiota

Hepatic fibrosis is intricately associated with dysregulation of gut microbiota and host metabolomes. Our previous studies have demonstrated that matrine can effectively reduce hepatosteatosis and associated disorders. However, it is poorly understood whether the gut microbiota involved in the attenuation of liver fibrosis by matrine. Herein we explored a novel mechanism of how oral administration of matrine alleviates liver fibrosis by modulating gut microbiota. Administration of matrine not only potently ameliorated liver fibrosis in carbon tetrachloride (CCl4)-induced mice, but also significantly preserved hepatic heat shock protein 72 (HSP72) in vivo and in vitro. Matrine was failed to reduce liver fibrosis when HSP72 upregulation was blocked by the HSP72 antagonist VER-155008. Also, consumption of matrine significantly alleviated gut dysbiosis and fecal metabonomic changes in CCl4-treated mice. Transplanted the faces of matrine-treated mice induced a remarkable upregulation of HSP72 and remission of fibrosis in liver in CCl4-exposed mice and inhibition of TGF-β1-induced inflammatory response and epithelial-mesenchymal transition (EMT) in AML-12 cells. Furthermore, deficiency of HSP72 partly reversed the intestinal microbial composition that prevented matrine from reducing CCl4-induced liver fibrosis in mice. This study reveals the "gut microbiota-hepatic HSP72" axis as a key mechanism of matrine in reducing liver fibrosis and suggest that this axis may be targeted for developing other new therapies for liver fibrosis.

Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and behavior, frequently accompanied by restricted and repetitive patterns of interests or activities. The gut microbiota has been implicated in the etiology of ASD due to its impact on the bidirectional communication pathway known as the gut-brain axis. However, the precise involvement of the gut microbiota in the causation of ASD is unclear. This study critically examines recent evidence to rationalize a probable mechanism in which gut microbiota symbiosis can induce neuroinflammation through intermediator cytokines and metabolites. To develop ASD, loss of the integrity of the intestinal barrier, activation of microglia, and dysregulation of neurotransmitters are caused by neural inflammatory factors. It has emphasized the potential role of neuroinflammatory intermediates linked to gut microbiota alterations in individuals with ASD. Specifically, cytokines like brain-derived neurotrophic factor, calprotectin, eotaxin, and some metabolites and microRNAs have been considered etiological biomarkers. We have also overviewed how probiotic trials may be used as a therapeutic strategy in ASD to reestablish a healthy balance in the gut microbiota. Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. It deems the repair of microbiota load would lower inflammatory chaos in the GI tract, correct neuroinflammatory mediators, and modulate the neurotransmitters to attenuate autism. The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder.

Polyphenols improve non-alcoholic fatty liver disease via gut microbiota: A comprehensive review.

Polyphenols, natural micronutrients derived from plants, are valued for their anti-inflammatory and antioxidant properties. The escalating global prevalence of non-alcoholic fatty liver disease (NAFLD) underscores its status as a chronic progressive liver condition. Furthermore, the dysregulation of gut microbiota (GM) is implicated in the onset and progression of NAFLD through the actions of metabolites such as bile acids (BAs), lipopolysaccharide (LPS), choline, and short-chain fatty acids (SCFAs). Additionally, GM may influence the integrity of the intestinal barrier. This review aims to evaluate the potential effects of polyphenols on GM and intestinal barrier function, and their subsequent impact on NAFLD. We searched through a wide range of databases, such as Web of Science, PubMed, EMBASE, and Scopus to gather information for our non-systematic review of English literature. GM functions and composition can be regulated by polyphenols such as chlorogenic acid, curcumin, green tea catechins, naringenin, quercetin, resveratrol, and sulforaphane. Regulating GM composition improves NAFLD by alleviating inflammation, liver fat accumulation, and liver enzymes. Furthermore, it improves serum lipid profile and gut barrier integrity. All of these components affect NAFLD through the metabolites of GM, including SCFAs, choline, LPS, and BAs. Current evidence indicates that chlorogenic acid, resveratrol, quercetin, and curcumin can modulate GM, improving intestinal barrier integrity and positively impacting NAFLD. More studies are necessary to evaluate the safety and efficacy of naringenin, sulforaphane, and catechin.

Nutritional Approaches Targeting Gut Microbiota in Oxidative-Stress-Associated Metabolic Syndrome: Focus on Early Life Programming.

Metabolic syndrome (MetS) denotes a constellation of risk factors associated with the development of cardiovascular disease, with its roots potentially traced back to early life. Given the pivotal role of oxidative stress and dysbiotic gut microbiota in MetS pathogenesis, comprehending their influence on MetS programming is crucial. Targeting these mechanisms during the early stages of life presents a promising avenue for preventing MetS later in life. This article begins by examining detrimental insults during early life that impact fetal programming, ultimately contributing to MetS in adulthood. Following that, we explore the role of oxidative stress and the dysregulation of gut microbiota in the initiation of MetS programming. The review also consolidates existing evidence on how gut-microbiota-targeted interventions can thwart oxidative-stress-associated MetS programming, encompassing approaches such as probiotics, prebiotics, postbiotics, and the modulation of bacterial metabolites. While animal studies demonstrate the favorable effects of gut-microbiota-targeted therapy in mitigating MetS programming, further clinical investigations are imperative to enhance our understanding of manipulating gut microbiota and oxidative stress for the prevention of MetS.

Cellular and Molecular Determinants of Biologic Drugs Resistance and Therapeutic Failure in Inflammatory Bowel Disease.

The advent of biologic drugs has revolutionized the treatment of Inflammatory Bowel Disease, increasing rates of response and mucosal healing in comparison to conventional therapies by allowing the treatment of corticosteroid-refractory cases and reducing corticosteroid-related side effects. However, biologic therapies (anti-TNFα inhibitors, anti-α4β7 integrin and anti-IL12/23) are still burdened by rates of response that hover around 40% (in biologic-naïve patients) or lower (for biologic-experienced patients). Moreover, knowledge of the mechanisms underlying drug resistance or loss of response is still scarce. Several cellular and molecular determinants are implied in therapeutic failure; genetic predispositions, in the form of single nucleotide polymorphisms in the sequence of cytokines or Human Leukocyte Antigen, or an altered expression of cytokines and other molecules involved in the inflammation cascade, play the most important role. Accessory mechanisms include gut microbiota dysregulation. In this narrative review of the current and most recent literature, we shed light on the mentioned determinants of therapeutic failure in order to pave the way for a more personalized approach that could help avoid unnecessary treatments and toxicities.

Inhibition of colon C5a/C5a receptor signalling pathway confers protection against LPS-induced acute kidney injury via gut microbiota-kidney axis

Acute kidney injury (AKI) is a critical condition often associated with systemic inflammation and dysregulated gut microbiota. This study aimed to investigate the effects of the C5a receptor antagonist W54011 on lipopolysaccharide (LPS)-induced AKI, focusing on the colon's C5a/C5a receptor pathway, intestinal barrier integrity, and gut microbiota. Our findings demonstrate that W54011 effectively ameliorated kidney injury in the LPS-induced AKI model by selectively inhibiting the colon's C5a/C5a receptor signalling pathway. Additionally, C5a receptor blockade resulted in the inhibition of colonic inflammation and the reconstruction of the intestinal mucosal barrier. Furthermore, W54011 administration significantly impacted the composition and stability of the gut microbiota, restoring the abundance of dominant bacteria to levels observed in the normal state of the intestinal flora and reducing the abundance of potentially harmful bacterial groups. In conclusion, W54011 alleviates LPS-induced AKI by modulating the interplay between the colon, gut microbiota, and kidneys. It preserves the integrity of the intestinal barrier and reinstates gut microbiota, thereby mitigating AKI symptoms. These findings suggest that targeting the colon and gut microbiota could be a promising therapeutic strategy for AKI treatment.

Quinoa alleviates osteoporosis in ovariectomized rats by regulating gut microbiota imbalance.

Postmenopausal osteoporosis (PMO) is associated with dysregulation of bone metabolism and gut microbiota. Quinoa is a grain with high nutritional value, and its effects and potential mechanisms on PMO have not been reported yet. Therefore, the purpose of this study is to investigate the bone protective effect of quinoa on ovariectomy (OVX) rats by regulating bone metabolism and gut microbiota. Quinoa significantly improved osteoporosis-related biochemical parameters of OVX rats and ameliorated ovariectomy-induced bone density reduction and trabecular structure damage. Quinoa intervention may repair the intestinal barrier by upregulating the expression of tight junction proteins in the duodenum. In addition, quinoa increased the levels of Firmicutes, and decreased the levels of Bacteroidetes and Prevotella, reversing the dysregulation of the gut microbiota. This may be related to estrogen signaling pathway, secondary and primary bile acid biosynthesis, benzoate degradation, synthesis and degradation of ketone bodies, NOD-like receptor signaling pathway and biosynthesis of tropane, piperidine and pyridine alkaloids. Correlation analysis showed that there is a strong correlation between gut microbiota with significant changes in abundance and parameters related to osteoporosis. Quinoa could significantly reverse the high intestinal permeability and change the composition of gut microbiota in OVX rats, thereby improving bone microstructure deterioration and bone metabolism disorder, and ultimately protecting the bone loss of OVX rats. © 2024 Society of Chemical Industry.

Combined exposure with microplastics increases the toxic effects of PFOS and its alternative F-53B in adult zebrafish

Microplastics (MPs) can adsorb and desorb organic pollutants, which may alter their biotoxicities. Although the toxicity of perfluorooctane sulfonate (PFOS) and its alternative 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) to organisms has been reported, the comparative study of their combined toxic effects with MPs on aquatic organisms is limited. In this study, adult female zebrafish were exposed to 10 μg/L PFOS/F-53B and 50 μg/L MPs alone or in combination for 14 days to investigate their single and combined toxicities. The results showed that the presence of MPs reduced the concentration of freely dissolved PFOS and F-53B in the exposure solution but did not affect their bioaccumulation in the zebrafish liver and gut. The combined exposure to PFOS and MPs had the greatest impact on liver oxidative stress, immunoinflammatory, and energy metabolism disorders. 16S rRNA gene sequencing analysis revealed that the combined exposure to F-53B and MPs had the greatest impact on gut microbiota. Functional enrichment analysis predicted that the alternations in the gut microbiome could interfere with signaling pathways related to immune and energy metabolic processes. Moreover, significant correlations were observed between changes in gut microbiota and immune and energy metabolism indicators, highlighting the role of gut microbiota in host health. Together, our findings demonstrate that combined exposure to PFOS/F-53B and MPs exacerbates liver immunotoxicity and disturbances in energy metabolism in adult zebrafish compared to single exposure, potentially through dysregulation of gut microbiota.

Bergenin Alleviates Ulcerative Colitis By Decreasing Gut Commensal Bacteroides vulgatus-Mediated Elevated Branched-Chain Amino Acids.

Ulcerative colitis is closely associated with the dysregulation of gut microbiota. There is growing evidence that natural products may improve ulcerative colitis by regulating the gut microbiota. In this research, we demonstrated that bergenin, a naturally occurring isocoumarin, significantly ameliorates colitis symptoms in dextran sulfate sodium (DSS)-induced mice. Transcriptomic analysis and Caco-2 cell assays revealed that bergenin could ameliorate ulcerative colitis by inhibiting TLR4 and regulating NF-κB and mTOR phosphorylation. 16S rRNA sequencing and metabolomics analyses revealed that bergenin could improve gut microbiota dysbiosis by decreasing branched-chain amino acid (BCAA) levels. BCAA intervention mediated the mTOR/p70S6K signaling pathway to exacerbate the symptoms of ulcerative colitis in mice. Notably, bergenin greatly decreased the symbiotic bacteria Bacteroides vulgatus (B. vulgatus), and the gavage of B. vulgatus increased BCAA concentrations and aggravated the symptoms of ulcerative colitis in mice. Our findings suggest that gut microbiota-mediated BCAA metabolism plays a vital role in the protective effect of bergenin on ulcerative colitis, providing novel insights for ulcerative colitis prevention through manipulation of the gut microbiota.

Effects of Guizhi and Erxian Decoction on menopausal hot flashes: insights from the gut microbiome and metabolic profiles.

To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes. 16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition. Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.

Nutritional modulation of gut microbiota in inflammatory bowel disease: a systematic review

Introduction: Inflammatory bowel diseases (IBD) have shown an increase in incidence worldwide. The pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microbiota (dysbiosis) and chronic inflammation develops as a result of poor dietary triggers. Diet plays an important role in modulating the gut microbiota and can be applied as a therapeutic tool to improve the course of the disease. Objective: It was to carry out a systematic review of the main interactions between nutrology, gut microbiota, and inflammatory bowel disease, to elucidate the main clinical outcomes of the disease after nutrological treatment, analyzing the main macro and micronutrients. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from August to October 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: 144 articles were found. A total of 39 articles were evaluated in full and 30 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 27 studies with a high risk of bias and 22 studies that did not meet GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2=59.9%&gt;50%. With nutritional treatment, several micronutrients have the potential to modulate intestinal inflammation. Immunonutrition has demonstrated its importance through vitamins A, C, E, and D, folic acid, beta-carotene, and trace elements such as zinc, selenium, manganese, and iron. The Specific Carbohydrate Diet, fermentable oligosaccharides, disaccharides, monosaccharides, and polyol diet, and the Mediterranean diet also appear to show strong anti-inflammatory properties and promise to improve symptoms of inflammatory bowel disease. Diet modulation can control IBD by reducing persistent intestinal symptoms, balancing the gut microbiota, and reducing markers of inflammation. Dietary therapy can improve the quality of life of IBD patients.

Porcine Intestinal Mucosal Peptides Target Macrophage-Modulated Inflammation and Alleviate Intestinal Homeostasis in Dextrose Sodium Sulfate-Induced Colitis in Mice.

Porcine intestinal mucosal proteins are novel animal proteins that contain large amounts of free amino acids and peptides. Although porcine intestinal mucosal proteins are widely used in animal nutrition, the peptide bioactivities of their enzymatic products are not yet fully understood. In the present study, we investigated the effect of porcine intestinal mucosal peptides (PIMP) on the RAW264.7 cell model of LPS-induced inflammation. The mRNA expression of inflammatory factors (interleukin 6, tumor necrosis factor-α, and interleukin-1β) and nitrous oxide levels were all measured by quantitative real-time PCR and cyclooxygenase-2 protein expression measured by Western blot. To investigate the modulating effect of PIMP and to establish a model of dextran sodium sulfate (DSS)-induced colitis in mice, we examined the effects of hematoxylin-eosin staining, myeloperoxidase levels, pro-inflammatory factor mRNA content, tight junction protein expression, and changes in intestinal flora. Nuclear factor κB pathway protein levels were also assessed by Western blot. PIMP has been shown in vitro to control inflammatory responses and prevent the activation of key associated signaling pathways. PIMP at doses of 100 and 400 mg/kg/day also alleviated intestinal inflammatory responses, reduced tissue damage caused by DSS, and improved intestinal barrier function. In addition, PIMP at 400 mg/kg/day successfully repaired the dysregulated gut microbiota and increased short-chain fatty acid levels. These findings suggest that PIMP may positively influence inflammatory responses and alleviate colitis. This study is the first to demonstrate the potential of PIMP as a functional food for the prevention and treatment of colitis.

Bifidobacterium bifidum alleviates adenine-induced acute kidney injury in mice by improving intestinal barrier function.

Acute kidney injury (AKI) is a kind of critical kidney disease characterized by tubular injury, rapid decline of renal function and renal inflammation, with high clinical incidence. AKI has been shown to be associated with dysregulation of the gut microbiota and impaired intestinal barrier. Bifidobacterium has a positive impact on the treatment of many diseases. However, little is known about the role and mechanism of Bifidobacterium in AKI. Based on previous experiments, Bifidobacterium bifidum FL228.1 and FL276.1, which can relieve intestinal inflammation, and Bifidobacterium bifidum ZL.1, which has anti-inflammatory potential, were screened. This study aimed to investigate the effects of Bifidobacterium bifidum FL228.1, FL276.1 and ZL.1 on AKI, focusing on their role in the gut microbiota composition and intestinal barrier function. Our results showed that Bifidobacterium bifidum FL228.1, FL276.1 and ZL.1 effectively improved kidney function in mice with AKI by regulating the gut microbiota dysregulation, inhibiting intestinal inflammation and rebuilding the intestinal mucosal barrier. In addition, intervention with probiotics turned the gut microbiota disturbance caused by AKI into a normalized trend, reversed the adverse outcome of microbiota imbalance, and increased the abundance of potentially beneficial bacteria Bifidobacterium and Faecalibaculum. In summary, Bifidobacterium bifidum FL228.1, FL276.1, and ZL.1 alleviate adenine-induced AKI based on the gut-kidney axis. Although their mechanisms of action are different, their effect on alleviating AKI is almost the same.

Danggui Buxue decoction regulates the immune function and intestinal microbiota of cyclophosphamide induced immunosuppressed mice.

Danggui Buxue decoction (DBD) is a traditional Chinese herbal formula. According to the theory of traditional Chinese medicine, the combination of Astragali Radix (AR) and Angelica sinensis (AS) is a classic prescription of tonifying qi and enriching blood. DBD has the functions of hematopoietic, immune enhancement and inflammation inhibition, usually used to treat qi and blood deficiency symptoms. Cyclophosphamide (CY) can inhibit humoral and cellular immunity, leading to the overall immune disorder of the body, resulting in immunosuppressive (IS). Pre-laboratory studies confirmed the immunomodulatory effects of DBD, but its mechanisms have not been thoroughly studied. In this study, the main purpose was to determine the effects of DBD on the immune function and intestinal mucosal barrier function of IS mice induced by CY, and initially explored the immunomodulatory mechanism of DBD. 100g of AR and 20g of AS were accurately weighed and 0.5g/mL of the DBD was obtained by boiling, filtration and rotary evaporation. Then, mice in the DBD group were administered 5g/kg of DBD by gavage, positive group were administered 40mg/kg of levamisole hydrochloride, whereas those in the control and model groups were given the corresponding volume of normal saline by gavage for 1week. At the end of the experiment, blood, spleen, thymus, ileum and cecum contents of all the experimental mice were collected aseptically. IS mouse model induced by intraperitoneal injection of 80mg/kg CY for three consecutive days. Pathomorphology was used to observe the physical barrier of the intestine, flow cytometry to detect splenic lymphocytes, immunohistochemistry to determine the content of intestinal barrier-associated proteins, ELISA to measure the secretion of ileal SIgA, qRT-PCR to detect the mRNA expression of immune-related genes in the intestine, and high-throughput sequencing and analysis of cecum contents. DBD alleviated spleen tissue damage and restored impaired immune functions, such as increased thymus index and CD4+/CD8+ subsets of spleen lymphocytes. In addition, DBD could increase ileum villi length and the ratio of villi length to crypt depth (V/C), and decrease crypt depth. Moreover, DBD administration up-regulated the expression of ZO-1, Occludin, Claudin-1, MUC-2 mRNA in ileum. And the secretions of sIgA and ZO-1 in ileum were also significantly improved. Furthermore, the administration of DBD can increase the diversity of gut microbiota, improve the composition of intestinal flora and increase the relative abundance of beneficial genus, such as Bacteroides. DBD alleviated CY-induced immune damage by decreasing the ratio of spleen index to CD4+/CD8+ of T lymphocyte subsets. And the intestinal barrier function of mice was by improves improving the intestinal morphology of the ileum and up-regulating the expression levels of ZO-1, MUC-2 and SIgA. DBD regulates CY-induced gut microbiota dysregulation in mice by increasing species diversity and richness, regulating the phylum, class and order levels of Bacteroidetes.

Gut microbiota defined epigenomes of Alzheimer's and Parkinson's diseases reveal novel targets for therapy.

The origins of Alzheimer's disease (AD) and Parkinson's disease (PD) involve genetic mutations, epigenetic changes, neurotoxin exposureand gut microbiota dysregulation. The gut microbiota's dynamic composition and its metabolites influence intestinal and blood-brain barrier integrity, contributing to AD and PD development. This review explores protein misfolding, aggregationand epigenetic links in AD and PD pathogenesis. It also highlights the role of a leaky gut and the microbiota-gut-brain axis in promoting these diseases through inflammation-induced epigenetic alterations. In addition, we investigate the potential of diet, probioticsand microbiota transplantation for preventing and treating AD and PD viaepigenetic modifications, along with a discussion related to current challenges and future considerations. These approaches offer promise for translating research findings into practical clinical applications.

Ento-A alleviates DSS-induced experimental colitis in mice by remolding intestinal microbiota to regulate SCFAs metabolism and the Th17 signaling pathway

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by changes in the metabolism of short chain fatty acids (SCFAs), dysregulation of gut microbiota, and an imbalance of Treg/Th17. Herein, we explore the effects of the Ento-A (an alcohol extract of Periplaneta americana L.) on a mouse model of UC. First, a chronic and recurrent UC model was constructed in BALB/c mice by 2.2% DSS administration. UC mice were continuously treated for 14 days with Ento-A (50, 100, 200 mg/kg, i.g.) or a negative control. Ento-A alleviated many of the pathological changes observed in UC mice, such as body weight loss, disease activity index, changes in colon length, and colonic mucosal damage index. Ento-A also decreased levels of proinflammatory cytokines (IL-1β, IL-6, IL-17A, and TNF-α), increased levels of anti-inflammatory cytokines (IL-10 and TGF-β1) and repaired the intestinal mucosal barrier. Additionally, Ento-A regulated the proportions of Th17 cells, and Treg cells in mesenteric lymph nodes harvested from treated mice (as assessed by Flow cytometry), and the expression levels of IL-17A and Foxp3 in colon (as assessed by immunohistochemistry). 16 S rRNA gene sequencing revealed that Ento-A regulated gut microbiota. GC-MS analysis demonstrated that Ento-A also restored SCFAs content in the intestinal tract. Finally, transcriptomic analysis revealed that Ento-A regulated the IL-17 signaling pathway. In summary, Ento-A regulates the diversity and abundance of intestinal flora in UC mice, enhancing the secretion of SCFAs, subsequently regulating the IL-17 signaling pathway, and ultimately repairing the intestinal mucosal barrier.